Effect of Sodium Ferulate on Human Colonic Anion Secretion and the Underlying Signaling Mechanism

Abstract

The present study investigated the effect of ferulic acid, a compound purified from traditional Chinese herbal medicine Chuanxiong and Awei, on anion secretion by human colonic cells (T₈₄) using the short circuit current (I_SC) and microspectrofluorimetric technique. Basolateral administration of sodium ferulate (SF) produced a concentration-dependent increase of I_SC in T₈₄ cells with an EC₅₀ of 1.2 mM. The SF-induced increase in I_SC contained a transient peak followed by a sustained plateau. Removal of extracellular Cl⁻, basolateral addition of bumetanide, an inhibitor of the Na⁺–K⁺–Cl⁻ cotransporter (NKCC) and apical pretreatment with DPC, a Cl⁻ channels blocker, decreased the SF-induced increase in I_SC by 94% (p<0.001), 84% (p<0.001) and 85% (p<0.001) respectively. Pretreatment with thapsigargin, a specific microsomal Ca²⁺-ATPase inhibitor, in combination with EGTA, a Ca²⁺ chelator, decreased the SF-induced peak by 52% (p<0.01) and inhibited the SF-induced plateau by 60% (p<0.05). Pretreatment with MDL12330A, an adenylate cyclase inhibitor, blocked the SF-induced I_SC plateau by 87% (p<0.01) but did not affect the SF-induced I_SC peak. Microspectrofluorimetric measurements show that SF induced a sustained increase in [Ca²⁺]_i. The results suggested that SF could induce Cl⁻ secretion in T₈₄ cells via Ca²⁺ and cAMP-dependent pathways.